The basic objectives of this proposal are to make creative contributions to the total synthesis of complex natural products of high physiological activity. The problems which are faced in this study relate to the synthesis of the neurotoxins, histrionicotoxin, and pumiliotoxon, which are principal components of skin secretions of the Colombian arrow-poison frog Dendrobates histrionicus, as well as the synthesis of the medicinally important alkaloids colchicine, lysergic acid, tylocrebine and related substances. These latter bases have shown high activity against various forms of cancer. In the course of this investigation we intend to incorporate new synthetic reactions and methodology that will be applicable beyond the scope of the defined projects.